MRN complex is an essential effector of DNA damage repair / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Genome stability can be threatened by both endogenous and exogenous agents. Organisms have evolved numerous mechanisms to repair DNA damage, including homologous recombination (HR) and non-homologous end joining (NHEJ). Among the factors associated with DNA repair, the MRE11-RAD50-NBS1 (MRN) complex (MRE11-RAD50-XRS2 in

Inherited NBN Mutations and Prostate Cancer Risk and Survival / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival. MATERIALS AND METHODS: Five thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q). RESULTS: The NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004). CONCLUSION: The NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q).

Expression of NBS1 in the salivary gland of radiation-injured rats / 中华放射医学与防护杂志

Objective To investigate the expressions of NBS1 mRNA and protein in the salivary gland of irradiated rats and explore the role of NBS1 in the repair of radiation injury of salivary gland epithelial cells.Methods Eighty rats were randomly divided into two groups for radiation and control (n =40 each).The rats were fractionally exposed to 3 Gy of 60Co γ-rays once in two days,leading to an accumulation dose of 3,6,9,12,15 Gy.The sham-irradiated controls were anesthetized in parallel but without irradiation.After 2-4 h of irradiation,the rats were sacrificed,IHC and RT-PCR were used to detect the expressions of NBS1 protein and mRNA in parotid and submandibular glands,and the ultra-structural changes in the glands were observed by a transmission electron microscopy.Results After irradiation,the salivary glands became atrophy and the parotid gland cells were damaged more serious than the submandibular gland cells.Compared with the controls,with the groups of dose,at 9,12,15 Gy in parotid gland (t =7.10,17.93,20.86,P ＜ 0.05),at 12,15 Gy in the submandibular gland (t =3.13,7.53,P ＜0.05),the expression of NBS1 mRNA was reduced.With the groups of dose at 9,12,15 Gy in paretid gland (t =4.29,17.91,91.29,P ＜ 0.05 ),the dose at 12,15 Gy in submandibular gland ( t =4.61,11.84,P＜0.05),the expression of NBS1 protein in serous cells,and the dose at 12,15 Gy in parotid gland ductal epithelial cell ( t =3.09,5.62,P ＜ 0.05) were reduced.But in the ductal epithelial cells as well as muoass cells in the submandibualr gland were steadily.Conclusions After irradiation,NBS1 at both protein and mRNA levels was dropped in the salivary gland of rats,which might contribute to the repair of radiation injury of salivary gland.

Study on the association between DNA double-strand break repair gene NBS1 polymorphisms and susceptibility on lung cancer / 中华流行病学杂志

Objective To study the association between DNA double-strand break repair gene NBS1(nijmegen breakage syndrome gene)polymorphisms and the susceptibility to lung cancer.Methods A case-control study design was applied.PCR-RFLP was used to identify NBS1 polymorphisms among 575 lung cancer cases and 575 controls.Results The frequencies of C/C,C/G and G/G genotypes at NBS1 rs 1805794 site were 25.9%,51.8%,22.3% among controls compared to 20.5%,52.3%,27.1% among cases.There was significant difference between controls and cases(χ~2=6.38,P=0.04).Individuals carrying C/G + G/G genotypes had an increased risk for lung cancer (OR=1.46,95%CI:1.09-1.97)compared to the C/C genotype.The frequencies of G/G,G/C and C/C genotypes at NBS1 rs2735383 site were 37.9%,47.0%,15.1% among controls compared to 35.5%,48.5%,16.0% among cases,with no significant difference between the two groups(χ~2=0.75,P=0.69).Individuals earning Hap4-GC haplotype(OR=1.70,95%CI:1.24-2.31)and Hap4/Hap2 dihaplotype(OR=1.75,95%CI:1.11-2.76)had an increased risk on lung cancer.Joint associations of smoking and the NBS1 polymorphism with the risk of lung cancer were observed(P＜0.05).Conclusion The G/G genotype at NBS1 rs1805794 site and the Hap4-GC haplotype and Hap4/Hap2 dihaplotype from rs1805794 and rs2735383 were both associated with lung cancer.

Construction and Identification of NBS1-targeting microRNA Expressing Eukaryotic Vector / 中国生物工程杂志

Objective:To construct NBS1 microRNA expressing eukaryotic recombinants,and identify biological activity of recombinants in Hela cell after transfection.Methods:According to sequence of NBS1mRNA,the NBS1 pre-microRNA was designed and synthesized,then cloned into the GFP reporter pcDNA6.2-GW/EmGFP-miR vector and transfected into Hela cell line.To detect integrity of inset fragment through colony PCR and sequencing analysis.The biological activity of recombinants through identify interference efficiency of NBS1 microRNA recombinants by way of Real-Time PCR and Western blot were determined.Results:Sequences of inset fragment in four microRNA expressing recombinants were correct.NBS1 mRNA and protein expression of four microRNA recombinants were decrease,which is the lowest in the NBS1mi-2 group.Conclusion:Four NBS1-targeting microRNA expressing recombinants all have biological activity in Hela cell line,and NBS1mi-2 recombinant has the most interference efficiency.The microRNA expressing plasmid which were successfully constructed and lay foundation for the studies on the tumor gene therapy of microrna targeting NBS1.